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O-linked ß-N-acetyl glucosamine (O-GlcNAc) is at the crossroads of cellular metabolism, including glucose and glutamine; its dysregulation leads to molecular and pathological alterations that cause diseases. Here we report that O-GlcNAc directly regulates de novo nucleotide synthesis and nicotinamide adenine dinucleotide (NAD) production upon abnormal metabolic states. Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, is O-GlcNAcylated by O-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. PRPS1 O-GlcNAcylation blocked AMPK binding and inhibited AMPK-mediated PRPS1 phosphorylation. OGT still regulates PRPS1 activity in AMPK-deficient cells. Elevated PRPS1 O-GlcNAcylation promotes tumorigenesis and confers resistance to chemoradiotherapy in lung cancer. Furthermore, Arts-syndrome-associated PRPS1 R196W mutant exhibits decreased PRPS1 O-GlcNAcylation and activity. Together, our findings establish a direct connection among O-GlcNAc signals, de novo nucleotide synthesis and human diseases, including cancer and Arts syndrome.
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Proteínas Quinases Ativadas por AMP , Processamento de Proteína Pós-Traducional , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Fosforilação , Glucose , Nucleotídeos/metabolismo , N-Acetilglucosaminiltransferases/genética , N-Acetilglucosaminiltransferases/metabolismoRESUMO
Biocatalysis has emerged as a powerful alternative to traditional chemical methods, especially for asymmetric synthesis. As biocatalysts usually exhibit excellent chemical, regio- and enantioselectivity, they facilitate and simplify many chemical processes for the production of a broad range of products. Here, a new biocatalyst called, R-selective amine transaminases (R-ATAs), was obtained from Mycobacterium sp. ACS1612 (M16AT) using in-silico prediction combined with a genome and protein database. A two-step simple purification process could yield a high concentration of pure enzyme, suggesting that industrial application would be inexpensive. Additionally, the newly identified and characterized R-ATAs displayed a broad substrate spectrum and strong tolerance to organic solvents. Moreover, the synthetic applicability of M16AT has been demonstrated by the asymmetric synthesis of (R)-fendiline from of (R)-1-phenylethan-1-amine.
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Aminas , Mycobacterium , Aminas/química , Transaminases/metabolismo , Especificidade por Substrato , BiocatáliseRESUMO
AIMS: Nucleotide de novo synthesis is essential to cell growth and survival, and its dysregulation leads to cancers and drug resistance. However, how this pathway is dysregulated in cancer has not been well clarified. This study aimed to identify the regulatory mechanisms of nucleotide de novo synthesis and drug resistance. METHODS: By combining the ChIP-Seq data from the Cistrome Data Browser, RNA sequencing (RNA-Seq) and a luciferase-based promoter assay, we identified transcription factor FOXK2 as a regulator of nucleotide de novo synthesis. To explore the biological functions and mechanisms of FOXK2 in cancers, we conducted biochemical and cell biology assays in vitro and in vivo. Finally, we assessed the clinical significance of FOXK2 in hepatocellular carcinoma. RESULTS: FOXK2 directly regulates the expression of nucleotide synthetic genes, promoting tumor growth and cancer cell resistance to chemotherapy. FOXK2 is SUMOylated by PIAS4, which elicits FOXK2 nuclear translocation, binding to the promoter regions and transcription of nucleotide synthetic genes. FOXK2 SUMOylation is repressed by DNA damage, and elevated FOXK2 SUMOylation promotes nucleotide de novo synthesis which causes resistance to 5-FU in hepatocellular carcinoma. Clinically, elevated expression of FOXK2 in hepatocellular carcinoma patients was associated with increased nucleotide synthetic gene expression and correlated with poor prognoses for patients. CONCLUSION: Our findings establish FOXK2 as a novel regulator of nucleotide de novo synthesis, with potentially important implications for cancer etiology and drug resistance.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Proliferação de Células , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genéticaRESUMO
BACKGROUND: Diabetes has become a prominent global public health problem, which is an important cause of death, disease burden, and medical and health economic burden. Previous studies have reported that majority of persons diagnosed with diabetes later presented with psychological and mental health diseases. The study aimed to explore the mediation role of anxiety on social support and depression among diabetic patents in elderly caring social organizations (SOs). METHODS: A multi-stage stratified cluster random sampling method was used in this cross-sectional study, and a questionnaire consisting of demographic questionnaire, MSPSS, GAD-7, and CES-D-10 was utilized to gather data. SPSS 22.0 and MPLUS 7.4 were used for statistical analysis. Spearman correlation analysis was employed to investigate correlations of key variables. A generalized linear model was used to exam factors associated with depression. Finally, the mediation effect among study variables was investigated by structural equation modeling (SEM). RESULTS: The average scores of social support, anxiety, and depression were 58.41 ± 14.67, 2.95 ± 3.95, and 7.24 ± 5.53, respectively. The factors of gender, social support, and anxiety were identified as significantly influential factors related to depression among diabetic patients in elderly caring SOs. The effect of social support on depression was significantly mediated by anxiety (ß = -0.467, 95%CI: -0.813 to -0.251). Furthermore, anxiety partially mediated the relationship between family support and depression (ß = -0.112, 95%CI: -0.229 to -0.012), and anxiety functioned as a complete mediator in the effect of significant others' support and depression (ß = -0.135, 95%CI: -0.282 to -0.024). CONCLUSIONS: The indirect effect of social support on depression through anxiety among diabetic patients in elderly caring SOs was elucidated. Social support played a key role in maintaining and regulating their mental health, particularly from family and significant others. Social support provided by both family and significant others exerted an important influence on maintaining and regulating their mental health. In light of this pathway, the elderly caring SOs should enhance the magnitude of social support from these two sources, thereby diminishing the likelihood of experiencing anxiety and depression.
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COVID-19 , Diabetes Mellitus , Humanos , Idoso , COVID-19/epidemiologia , Estudos Transversais , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/etiologia , Pandemias , Ansiedade/epidemiologia , Ansiedade/diagnóstico , Apoio Social , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , China/epidemiologiaRESUMO
The aim of this study was to characterize the effects of cornstalk biomass amendments on microbial communities in bauxite residues (BRs) by phylogenetic analysis. Improvements in soil geochemical, physical, and biological properties were assessed to identify the major factors controlling microbial community development in BRs. After one year of incubation, the salinity and structure of the amended BRs had gradually improved, with pH dropping from 11.39 to 9.89, the exchangeable sodium percentage (ESP) dropping from 86.3% to 35.2%, and the mean weight diameter (MWD) rising from 0.12 mm to 0.38 mm. Further analysis of community level physiological profiles (CLPP) showed that the microbial utilization of different carbohydrates had shifted significantly, in addition to increases in the diversity index H' (0.7-7.34), U (2.16-3.14), and the average well color development (0.059-1.08). Over the one-year outside incubation, the dominant fungal phyla in the BRs had shifted gradually from Ascomycota (85.64%) to Ascomycota (52.07%) and Basidiomycota (35.53%), while the dominant bacterial phyla had shifted from Actinobacteria (38.47%), Proteobacteria (21.39%), and Gemmatimonadetes (12.72%) to Actinobacteria (14.87%), Proteobacteria (23.53%), and Acidobacteria (14.37%). Despite these shifts, microbial diversity remained lower in the amended BRs than in the natural soil. Further redundancy analysis indicated that pH was the major factor driving shifts in the bacterial community, while aggregates were the major factor driving shifts in the fungal community. This study demonstrated that amendment with cornstalk biomass shifted the microbial community in the BRs from halophilic groups to acidogenic groups by improving the soil environmental conditions.
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Microbiota , Microbiologia do Solo , Óxido de Alumínio/química , Biomassa , Filogenia , Solo/químicaRESUMO
The fungal community and soil geochemical, physical and biological parameters were analyzed, respectively, in bauxite residues (BRs) treated with organic matter and vermiculite/fly ash by phylogenetic analysis of ITS-18 S rRNA, community level physiological profiles (CLPP) and so on. The results indicated that after amendment of the BR, microbial utilization of carbohydrates and their enzyme activities were significantly increased, but fungal compositions at the phylum level were similar and dominated by the phylum of Ascomycota (82.05-98.96%, RA: relative abundance) after one year of incubation. The fungal taxa in the amended BR treatments, however, show significantly less alpha and beta diversity compared with the reference soils, although they still harbor a substantial novel taxon. The combined amendment of organic matter (OM) and vermiculite/fly ash significantly increases the fungal taxa at the genus and species level compared with solely OM amendment. The results of the following canonical correspondence analysis found that, over 90% variation of the fungal community could be explained by pH, OM and mean weight diameter (MWD) of aggregates; but the biological indicators, including urease (UR), dehydrogenase (DHA) and the value of average well color development (AWCD) could explain only 50% variation of the fungal flora in BRs. This paper indicated that resilience of fungal community in BRs was positively correlated with the BRs' improvement in fertility as well as biogeochemical properties, but alkalinity must be firstly decreased to the target level of BRs' rehabilitation.
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Cinza de Carvão , Microbiologia do Solo , Óxido de Alumínio , Silicatos de Alumínio , Filogenia , SoloRESUMO
Mammalian ovarian follicular development is an intricate, elaborate, and well-organized phenomenon regulated by various signaling pathways; however, the underlying mechanism remains unclear. Mammalian sirtuins (sirtuin 1 to sirtuin 7) are a group of NAD+ -dependent deacetylases implicated in various physiological processes including cell proliferation, apoptosis, cell cycle progression, and insulin signaling. Mammalian ovarian sirtuins have been studied using adult and aged bovine, porcine, and murine models. However, limited information is available regarding their precise expression patterns and the localization of follicle development in mice. This study aimed to assess the dynamic expression and localization of all seven sirtuins in early postnatal mouse ovaries through real-time polymerase chain reaction analysis and immunohistochemistry, respectively. During postnatal ovarian follicle development, sirtuin 1, sirtuin 4, and sirtuin 6 were downregulated compared with those in 1-day postnatal mouse ovaries (p < .05), indicating that these three sirtuin genes may be markers of follicular development. Combining their localization in granulosa cells through immunohistochemical studies, sirtuin 1, sirtuin 4, and sirtuin 6 are suggested to play negative regulatory roles in mammal ovarian follicular granulosa cell development. Furthermore, we found that sirtuin 2 (p < .05) and sirtuin 7 (p < .05) mRNA were constantly upregulated relative to sirtuin 1, although limited information is available regarding sirtuin 7. Among all sirtuins in mouse ovaries, sirtuin 1 was relatively and steadily downregulated. Upon sirtuin 1 overexpression in 1-day postnatal mouse ovaries via sirtuin 1-harboring adenoviruses in vitro, the emergence of primary follicles was delayed, as was the emergence of secondary follicles in 4-day postnatal ovaries. Further studies on KGN cell lines reported that interfering with sirtuin 1 expression in granulosa cell significantly affected granulosa cell proliferation and the expression of mitochondrial genes. This study presents the first systemic analysis of dynamic patterns of sirtuin family expression in early postnatal mice ovaries, laying the foundation for further studies on less discussed sirtuin subtypes, such as sirtuin 5 and sirtuin 7.
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Folículo Ovariano/metabolismo , Sirtuínas/genética , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Animais Recém-Nascidos , Células Cultivadas , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Regulação Enzimológica da Expressão Gênica , Camundongos , Camundongos Endogâmicos ICR , Folículo Ovariano/enzimologia , Ovário/crescimento & desenvolvimento , Ovário/metabolismo , Sirtuínas/metabolismoRESUMO
There are the two major pathways responsible for the repair of DNA double-strand breaks (DSBs): non-homologous end-joining (NHEJ) and homologous recombination (HR). NHEJ operates throughout the cell-cycle, while HR is primarily active in the S/G2 phases suggesting that there are cell cycle-specific mechanisms that regulate the balance between NHEJ and HR. Here we reported that CDK2 could phosphorylate RNF4 on T26 and T112 and enhance RNF4 E3 ligase activity, which is important for MDC1 degradation and proper HR repair during S phase. Mutation of the RNF4 phosphorylation sites results in MDC1 stabilization, which in turn compromised HR during S-phase. These results suggest that in addition to drive cell cycle progression, CDK also targets RNF4, which is involved in the regulatory network of DSBs repair.
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Quinase 2 Dependente de Ciclina/metabolismo , Proteínas Nucleares/metabolismo , Reparo de DNA por Recombinação , Fase S/genética , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Ciclo Celular , Linhagem Celular , Quebras de DNA de Cadeia Dupla , Proteínas Nucleares/química , Fosforilação , Sumoilação , Transativadores/metabolismo , Fatores de Transcrição/químicaRESUMO
BACKGROUND: Older adults living in elderly caring social organizations (SOs) are prone to suffer from depression. Many studies have found correlations between environmental and quality-of-life factors and depression; however, evidence from elderly caring SOs is rare, particularly in China. METHODS: A cross-sectional study was conducted among service recipients in elderly caring SOs in Anhui and Chongqing, China. Data on demographic and health-related characteristics, living environment factors, and service quality satisfaction factors in 2171 older adults were used for analysis. The binary logistic regression model was conducted to estimate the association between living environment and service quality satisfaction factors and depression. RESULTS: Our results indicated that living environment factors in terms of exposure to suitable temperature and humidity (OR = 0.655; 95 % CI: 0.446, 0.963), green coverage >30 % (OR = 0.432; 95 % CI: 0.337, 0.553) were associated with lower odds of developing depression. Also, an opposite relationship was found in the noise factor (OR = 1.985; 95 % CI: 1.395, 2.823). Higher satisfaction with admission and discharge services, dietary services, entertainment services, and psychological support services were also found to be associated with a lower risk of depression. LIMITATIONS: A cross-sectional design precluded determining whether living environment, service quality satisfaction, and depression are causally related. Measurement of living environment factors and service quality satisfaction factors needs to be further clarified comprehensively. CONCLUSIONS: Enhancing the living environment and the quality of the services provided to seniors in the elderly caring SOs is conducive to the reduction of the likelihood of depression.
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Depressão , Humanos , Idoso , Masculino , Feminino , Estudos Transversais , China/epidemiologia , Depressão/epidemiologia , Depressão/psicologia , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Meio Social , Satisfação Pessoal , Cuidadores/psicologia , População do Leste AsiáticoRESUMO
Aging is a challenge to global development. This challenge is particularly significant for China because it has the largest elderly population worldwide. The proportion of aging population continues to increase, and solely relying on government efforts to meet the needs of the elderly is inadequate. Hence, involvement of social organizations in elderly care services is needed. Their core members exhibit higher sense of responsibility and identification with the organization than regular members, thus profoundly affecting organizational development. Based on the Social Capital Theory, this study employed a multistage stratified random sampling method to examine the social capital stock of elderly social organizations and their core members across six cities in Anhui Province, China. Chi-square tests analyzed the relationship between the core members' demographic factors and individual performance. Independent-sample t-tests assessed the relationship between social capital and individual performance. Finally, binary logistic regression models determined the factors influencing the individual performance of core members. Social networks within core members' social capital and the internal social capital of elderly caring social organizations (ESOs) affect the individual performance of core members. Therefore, organizations should provide more training opportunities for core members to expand their networks. Cultivating a shared language and vision as components of social capital can enhance organizational cohesion and operational stability.
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Capital Social , China , Humanos , Idoso , Masculino , Feminino , Pessoa de Meia-IdadeRESUMO
Introduction: Realgar has a long history ofuse in traditional medicines. However, the mechanism through which Realgar or Realgar-Indigo naturalis formula (RIF) exert therapeutic effects is only partially understood. Methods: In this study, 60 feces and 60 ileum samples from rats administered with realgar or RIF were collected to examine the gut microbiota. Results: The results showed that realgar and RIF influenced different microbiota in both feces and ileum. Compared with realgar, RIF at low dosage (0.1701 g/3 ml) significantly increased the microbiota diversity. LEfSe and random forest analyses showed that the bacterium Bacteroidales was significantly altered after RIF administration, and it was predicted that these microorganisms contribute to the inorganic arsenic metabolic process. Discussion: Our results suggest that realgar and RIF may exert their therapeutic effects through influencing microbiota. The low dose of RIF had greater effects on increasing the diversity of microbiota, and Bacteroidales in feces might participate in the inorganic arsenic metabolic process to exert therapeutic effects for realgar.
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BACKGROUND: Follicular development in mammalian ovaries is a complex and dynamic process, and the interactions and regulatory-feedback loop between the follicular microenvironment, granulosa cells (GCs), and oocytes can affect follicular development and normal ovary functions. Abnormalities in any part of the process may cause abnormal follicular development, resulting in infertility. Hence, exploring the pathogenesis of abnormal follicular development is extremely important for diagnosing and treating infertile women. METHODS: RNA sequencing was performed with ovarian cortical tissues established in vitro. In situ-hybridization assays were performed to study microRNA-338-3p (miR-338-3p) expressed in GCs and oocytes. In vitro culture models were established with GCs and neonatal mouse ovaries to study the biological effects of miR-338-3p. We also performed in vivo experiments by injecting adeno-associated virus vectors that drive miR-338-3p overexpression into the mouse ovarian bursae. RESULTS: Sequencing analysis showed that miR-338-3p was expressed at significantly higher levels in ovarian cortical tissues derived from patients with ovarian insufficiency than in cortical tissues derived from patients with normal ovarian function; miR-338-3p was also significantly highly expressed in the GCs of patients with diminished ovarian reserve (P < 0.05). In situ-hybridization assays revealed that miR-338-3p was expressed in the cytoplasm of GCs and oocytes. Using in vitro culture models of granulosa cells, we found that miR-338-3p overexpression significantly suppressed the proliferation and oestradiol-production capacity of GCs (P < 0.05). In vitro culture models of neonatal mouse ovaries indicated that miR-338-3p overexpression suppressed the early follicular development in mouse ovaries. Further analysis revealed that miR-338-3p might be involved in transforming growth factor ß-dependent regulation of granulosa cell proliferation and, thus, early follicular development. Injecting miR-338-3p-overexpression vectors into the mouse ovarian bursae showed that miR-338-3p down-regulated the oocyte mitochondrial membrane potential in mice and disrupted mouse oestrous cycles. CONCLUSION: miR-338-3p can affect early follicular development and normal ovary functions by interfering with the proliferation and oestradiol production of GCs. We systematically elucidated the regulatory effect of miR-338-3p on follicular development and the underlying mechanism, which can inspire new studies on the diagnosis and treatment of diseases associated with follicular development abnormalities.
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Infertilidade Feminina , MicroRNAs , Doenças Ovarianas , Feminino , Humanos , Animais , Camundongos , Oócitos , Estradiol , Células da Granulosa , MicroRNAs/genética , MamíferosRESUMO
As a type of emerging pollutant of concern, organophosphate esters (OPEs) have posed a moderate risk to the remote Antarctic waters. Triphenyl phosphate (TPHP) is a common type of OPEs in water, which has been proven to have toxic effects, bioaccumulation, and amplification effects and pose a great threat to the environment and human health. Fourier transform infrared spectroscopy (FT-IR) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to investigate the degradation process of TPHP in three advanced oxidation processes (UV-AOPs), including ultraviolet-hydrogen peroxide (UV-H2O2), ultraviolet-titanium dioxide (UV-TiO2), and ultraviolet-persulfate (UV-PS) systems. This was the first instance of using FT-IR for the online observation of the change in infrared characteristic peaks in the degradation process of TPHP, and its degradation reaction kinetics, photodegradation products, and degradation pathways were analyzed. The results showed that TPHP could be effectively degraded under UV-H2O2, UV-TiO2, and UV-PS systems, and the photodegradation half-lives were 74, 150, and 89 min, respectively. The UV-H2O2 system had the best degradation effect on TPHP. Additionally, the degradation reactions of TPHP in three systems conformed to the first-order kinetics. When the concentration of H2O2 was 0-0.097 mol·L-1, the increase in H2O2 concentration promoted the degradation of TPHP, and when the concentration of TiO2 was 0-0.013 mol·L-1, the increase in TiO2 concentration promoted the degradation of TPHP. The photodegradation pathway of TPHP mainly included the P-O-C bond breaking, the C-H bond cleavage of the benzene ring structure and the hydrolysis reaction of TPHP. The UV-H2O2 system was used to degrade OPEs in the environmental water of Chengdu, and it was found that the removal rate of TPHP was 66% when the water samples of the park landscape water were degraded for 60 min.
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Peróxido de Hidrogênio , Água , Humanos , Peróxido de Hidrogênio/química , Cromatografia Líquida , Espectroscopia de Infravermelho com Transformada de Fourier , Raios Ultravioleta , Espectrometria de Massas em Tandem , OrganofosfatosRESUMO
BACKGROUND: The mammalian follicle is the basic functional unit of the ovary, and its normal development is required to obtaining oocytes capable of fertilization. As women get older or decline in ovarian function due to certain pathological factors, the growth and development of follicles becomes abnormal, which ultimately leads to infertility and other related female diseases. Kuntai capsules are currently used in clinical practice to improve ovarian function, and they contain the natural compound Baicalin, which is a natural compound with important biological activities. At present, the role and mechanism of Baicalin in the development of ovarian follicles is unclear. METHODS: Human primary granulosa cells collected from follicular fluid, and then cultured and treated with Baicalin or its normal control, assessed for viability, subjected to RT-PCR, western blotting, flow cytometry, and hormone analyses. The estrus cycle and oocytes of CD-1 mice were studied after Baicalin administration and compared with controls. Ovaries were collected from the mice and subjected to hematoxylin-eosin staining and immunohistochemistry analysis. RESULTS: We showed that Baicalin had a dose-dependent effect on granulosa cells cultured in vitro. A low concentration of Baicalin (for example, 10 µM) helped to maintain the viability of granulosa cells; however, at a concentration exceeding 50 µM, it exerted a toxic effect. A low concentration significantly improved the viability of granulosa cells and inhibited cell apoptosis, which may be related to the resultant upregulation of Bcl-2 expression and downregulation of Bax and Caspase 3. By constructing a hydrogen peroxide-induced cell oxidative stress damage model, we found that Baicalin reversed the cell damage caused by hydrogen peroxide. In addition, Baicalin increased the secretion of estradiol and progesterone by upregulating P450arom and stAR. The results of the in vivo experiment showed that the intragastric administration of Baicalin to aged mice improved the estrous cycle and oocyte quality. Furthermore, we observed that Baicalin enhanced the viability of granulosa cells through the mTOR pathway, which in turn improve ovarian function. CONCLUSION: These results indicate that Baicalin could improve the viability of ovarian granulosa cells and the secretion of steroid hormones and thus could help to improve degenerating ovarian function and delay ovarian aging.
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Flavonoides , Células da Granulosa , Ovário , Serina-Treonina Quinases TOR , Animais , Feminino , Flavonoides/farmacologia , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/enzimologia , Humanos , Camundongos , Ovário/efeitos dos fármacos , Ovário/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismoRESUMO
Aging could be critical in limiting the application of subcutaneous adipose tissue (SAT) in tissue repair and reconstruction. However, no systematic study on the characteristics of SAT aging has been conducted. In this study, a scanning electronic microscope was used to detect the structural and compositional changes of SAT collected from nine females in three age groups. Multi-omics data of SAT from 37 females were obtained from Gene Expression Omnibus database, and 1860 genes, 56 miRNAs, and 332 methylated genes were identified as being differentially expressed during aging among non-obese females. Using Weighted Correlation Network Analysis (WGCNA), 1754 DEGs were defined as aging-associated genes for non-obese females, distributed among ten co-expression modules. Through Gene Ontology enrichment analysis and Gene Set enrichment analysis on those aging-associated DEGs, SAT aging was observed to be characterized by variations in immune and inflammatory states, mitochondria, lipid and carbohydrate metabolism, and regulation of vascular development. SUPV3L1, OGT, and ARPC1B were identified as conserved and core SAT-aging-related genes, as verified by RT-qPCR among 18 samples in different age groups. Multi-omics regulatory networks of core aging-associated biological processes of SAT were also constructed. Based on WGCNA, we performed differential co-expression analysis to unveil the differences in aging-related co-expression patterns between obese and non-obese females and determined that obesity could be an important accelerating factor in aging processes. Our work provides a landscape of SAT aging, which could be helpful for further research in fields such as repair and reconstruction as well as aging.
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Envelhecimento/metabolismo , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Obesidade/metabolismo , Gordura Subcutânea/metabolismo , Transcriptoma , Envelhecimento/genética , Feminino , Humanos , Obesidade/genéticaRESUMO
Realizing both high gravimetric and volumetric specific capacitances (noted as CW and CV, respectively) is an essential prerequisite for the next-generation, high performance supercapacitors. However, the need of electronic/ionic transport for electrochemical reactions causes a "trade-off" between compacted density and capacitance of electrode, thereby impairing gravimetric or volumetric specific capacitances. Herein, we report a high-performance, film-based supercapacitor via a thermal reduction of graphene oxide (GO) in air. The reduced, layer-structured graphene film ensures high electrode density and high electron conductivity, while the hierarchical channels generated from reduction-induced gas releasing process offer sufficient ion transport pathways. Note that the resultant graphene film is employed directly as electrodes without using any additives (binders and conductive agents). As expected, the as-prepared electrodes perform particularly well in both CW (420F g-1) and CV (360F cm-3) at a current density of 0.5 A g-1. Even at an ultrahigh current density of 50 A g-1, CW and CV maintain in 220F g-1 and 189F cm-3, respectively. Furthermore, the corresponding symmetric two-electrode supercapacitor achieves both high gravimetric energy density of 54 W h kg-1 and high gravimetric power density of 1080 W kg-1, corresponding to volumetric energy density of 46 W h L-1 and volumetric power density of 917 W L-1.
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Hydrogen is one of the most promising sustainable energy carriers for its high gravimetric energy density and abundance. Nowadays, hydrogen production and storage are the main constraints for its commercialization. As a current research focus, hydrogen production from methanol-water reforming, especially at low temperature, is particularly important. In this study, a novel reaction path for low-temperature methanol reforming through synergistic catalysis was developed. Alcohol dehydrogenase (ADH) and coenzyme I (nicotinamide adenine dinucleotide, NAD+ ) were employed for methanol catalytic dehydrogenation at low temperature, which could generate formaldehyde and reductive coenzyme I (NADH). Covalent triazine framework-immobilized ruthenium complex (Ru-CTF) was prepared afterwards. On one hand, the catalyst exhibited high activity for the formaldehyde-water shift reaction to generate hydrogen and carbon dioxide. On the other hand, the NADH dehydrogenation was also catalyzed by the Ru-CTF, producing NAD+ and hydrogen. Additionally, the catalyst also showed high biocompatibility with ADH. Through the synergistic effect of the above two main processes, methanol could be converted into hydrogen and carbon dioxide stably at low temperature for more than 96â h. The hydrogen production rate was dependent on the pH of the reaction solution as well as the ADH dosage. A hydrogen production rate of 157â mmol h-1 mol-1 Ru was achieved at the optimum pH (8.1). Additionally, the hydrogen production rate increased linearly with the ADH dosage, reaching 578â mmol h-1 mol-1 Ru when the ADH dosage was 180â U at 35 °C. This research could not only help overcome the difficulties for methanol reforming near room temperature but also give new inspiration for designing new reaction pathways for methanol reforming.
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Álcool Desidrogenase/química , Complexos de Coordenação/química , Rutênio/química , Dióxido de Carbono/química , Catálise , Temperatura Baixa , Formaldeído/química , Hidrogênio/química , Cinética , Metanol/química , Modelos Químicos , NAD/química , Oxirredução , Propriedades de Superfície , Termodinâmica , Triazinas/química , Água/químicaRESUMO
The large-scale development of animal husbandry and the wide agricultural application of livestock manure lead to more and more serious co-pollution of heavy metals and antibiotics in soil. In this study, two common feed additives, copper (Cu) and sulfadiazine (SDZ), were selected as target pollutants to evaluate the toxicity and interaction of antibiotics and heavy metals on ammonia oxidizers diversity, potential nitrification rate (PNR), and enzymatic activity in black soils. The results showed that soil enzyme activity was significantly inhibited by single Cu pollution, but the toxicity could be reduced by introducing low-concentration SDZ (5 mg · kg-1), which showed an antagonistic effect between Cu and SDZ (5 mg · kg-1), while the combined toxicity of high-concentration SDZ (10 mg · kg-1) and Cu were strengthened compared with the single Cu contamination on soil enzymes. In contrast, soil PNR was more sensitive to single Cu pollution and its combined pollution with SDZ than the enzyme activity. Real-time fluorescence quota PCR and Illumina Hiseq/Miseq sequencing results showed that ammonia-oxidizing archaea (AOA) was decreased in C2 (200 mg · kg-1 Cu treatment) and ammonia-oxidizing bacteria (AOB) was obviously stimulated in soil contaminated in C2, while in S5 (5 mg · kg-1 SDZ treatment), AOB was decreased; both AOA and AOB were significantly decreased at gene level in soils with combined pollutants (C2S5, 200 mg · kg-1 Cu combined with 5 mg · kg-1 SDZ). So, it can be concluded that combined pollution can cause more serious toxicity on the enzymatic activity, PNR, and ammonia-oxidizing microorganisms in soil through the synergistic effect between heavy metals and antibiotics pollutants.
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Amônia , Archaea , Animais , Bactérias , Cobre , Nitrificação , Oxirredução , Solo , Microbiologia do Solo , SulfadiazinaRESUMO
BACKGROUNDS: Long non-coding RNA is a novel group of non-protein coding transcripts over 200 nt in length. Recent studies have found that they are widely involved in many pathological and physiological processes. In our previous study, we found that lnc-GULP1-2:1 was significantly down-regulated in the ovarian cortical tissue of patients with primary ovarian insufficiency and predicted that lnc-GULP1-2:1 has a regulatory effect on COL3A1. RESULTS: In this study, we found that lnc-GULP1-2:1 was mainly localized in the cytoplasm of luteinized granulosa cells. The expression of lnc-GULP1-2:1 was lower in patients with diminished ovarian reserve but substantially elevated in patients with polycystic ovary syndrome. Overexpression of lnc-GULP1-2:1 in KGN cells significantly inhibited cell proliferation, likely through cell cycle related genes CCND2 and p16. Moreover, lnc-GULP1-2:1 expression was positively correlated with the level of COL3A in luteinized granulosa cells from patients with different ovarian functions as well as in multiple cell lines. Overexpression of lnc-GULP1-2:1 in KGN cells promoted the expression of COL3A1 and its translocation into the nucleus. Consistently, silencing COL3A1 in KGN cells also significantly inhibited cell proliferation. CONCLUSIONS: Lnc-GULP1-2:1 affects the proliferation of granulosa cells by regulating the expression and localization of COL3A1 protein, and may participate in the regulation of ovarian follicle development. This study will provide new insight into molecular mechanisms underlying ovarian follicular development, which will help generate novel diagnostic and therapeutic strategies for diseases related to ovarian follicular development disorders.
Assuntos
Colágeno Tipo III/metabolismo , Células da Granulosa/metabolismo , RNA Longo não Codificante/genética , Proliferação de Células , Feminino , HumanosRESUMO
Calcium is a crucial factor in regulating the biological behavior of cells. The imbalance of calcium homeostasis in cytoplasm will cause abnormal behavior of cells and the occurrence of diseases. In intracytoplasmic sperm injection (ICSI) cycle, the dysfunction of oocyte activation caused by insufficient release of Ca2+ from endoplasmic reticulum is one of the main reasons for repeated fertilization failure. Calcium ionophore (A23187) is a highly selective calcium ionophore, which can form stable complex with Ca2+ and pass through the cell membrane at will, effectively increasing intracellular Ca2+ levels. It has been reported that calcium ionophore (A23187) can activate oocytes and obtain normal embryos. However, there are few studies on unfertilized oocytes after calcium ionophore (A23187) rescue activation in ICSI cycle. The purpose of this study was to analyze the effects of calcium ionophore (A23187) rescue activation on the activation of unfertilized oocytes, embryonic development potential, embryonic development timing and chromosomal aneuploidy, and to compare and analyze the clinical data of patients with calcium ionophore (A23187) activation in clinical application. The results showed that a certain proportion of high-quality blastocysts with normal karyotype could be obtained after calcium ionophore (A23187) rescue activation of unfertilized oocytes, and it did not have a significant effect on the timing of embryo development. In clinical practice, direct activation with calcium ionophore (A23187) after ICSI was better than rescue activation the next day. In conclusions, the studies on the effectiveness and safety of calcium ionophore (A23187) rescue activation for oocytes with ICSI fertilization failure can enable some patients to obtain usable, high-quality embryos during the first ICSI cycle.